14 replies to this topic

[eon]

What I mean by this is that all diseases/disorders have a name so they fit in a category and can be assigned a medication that fits in for that category.

 

No pharmaceuticals would say it's a problem in the dopamine system so take dopaminergics, they'll say here's a new drug for this new disease/disorder. Take it!

 

So DRD4 (dopamine receptor D4) is linked with ADHD, in other words ADHD is a dopamine problem. Which could mean taking anything dopaminergic (natural or prescription) could have effects. I feel as if Kava has helped me get things done. It is listed as a DRI but I would think something that directly affects D4 would be more promising.

 

"Mutations in this gene have been associated with various behavioral phenotypes, including autonomic nervous system dysfunction, attention deficit/hyperactivity disorder,^[4]schizophrenia,^[5] and the personality trait of novelty seeking.^[6]"

 

"The 'DRD4 long' variant, or more specifically the 7 repeat (7R), has been linked to a susceptibility for developing ADHD in several meta-analyses ^[9] [10] and other psychological traits and disorders."

 

http://en.wikipedia....ine_receptor_D4

 

There are some interesting lists of agonists and antagonists in that page if anyone here know more about them. They're mostly if not all, chemicals and or prescription drugs though. If anyone here know of a natural herb that affects DRD4 directly, what is it?

 

Does a DRI actually benefit all the dopamine receptors as a whole and not specific?

Edited by eon, 10 March 2015 - 07:02 PM.

[Mind_Paralysis]

Yes, a DRI affects all of the dopamine-receptors simultaneously, since it increases the overall level of dopamine in your entire brain.

The problem is that pretty much all DRI's also happen to be NRI's, they increase norepinephrine as well...

 

And ADHD is most likely, as you have surmised, a problem related to the Dopamine and NMDA -networks in the brain, not the norepinephrinergic ones.

Affecting Nore and every D-receptor, even tho' not every part of the circuitry is dysfunctional, gives pretty severe side-effects - mainly because you don't NEED to affect those parts of your brain. The result is regulation of a few parts, but a pretty massive dysregulation of other parts.

 

DRD4 -agonists is a very interesting potential area of research, and they've been discussed here on Longecity before.

You can read about the most selective DRD4 -agonist here:

A-412997 (Dopamine D4 agonist ) Dopamine rDOPAMINE RECEPTOR SENSITIVITY - Brain Health - LONGECITY

However, that compound, even tho' it has shown potential as a treatment, has ONE single noticeable side-effect: Excessive penile erection. It gives you a never-ending, almost painful to some, boner.

If you're a woman - NO PROBLEMO!! : D It is the perfect drug... If you're a man... eh, well, not necessarily.

[eon]

Well that must be dose dependent I'd assume. Also, where did those people who tried it get theirs? 

 

Would the DRIs listed on wikipedia that are natural lack the norepinephrine activity? I'd have to look into it but when I skimmed through it I see nothing relating to having any effect on it.

 

Other DRIs[edit]

• Chaenomeles speciosa (Flowering Quince)^[9]
• Oroxylin A (found in Oroxylum indicum and Scutellaria baicalensis (Skullcap))^[10]
• Kavain and desmethoxyyangonin (possibly) (found in Piper methysticum (Kava))

 

http://en.wikipedia....ptake_inhibitor

 

BTW, I may have found the cure for my unmotivation in Kava but my "novelty seeking" DRD4 "defect" seems to make me want to seek out more shit I think I need to try out. LOL. You should see my cabinet full of drugs and supplements!

Edited by eon, 10 March 2015 - 09:11 PM.

[AlwaysLearning]

My impression these days is that there are multiple mutations that can cause the symptoms we collectively call "ADHD". My recollection about the DRD4 receptor is that a known mutation confers a sort of resistance to ADHD, in that people with that mutation have a milder form of the disorder than people with the most common allele. Given that the prefrontal cortex is the "newest" part of the brain, one might reasonably expect it to be the most "buggy" or "volatile" - in the sense of being most sensitive to common mutations - and may still be rather actively evolving. Under-activity of the PFC may have many etiologies but from what I understand, the resulting effects generally include ones commonly ascribed to ADHD.

[Mind_Paralysis]

Well that must be dose dependent I'd assume. Also, where did those people who tried it get theirs? 

 

Would the DRIs listed on wikipedia that are natural lack the norepinephrine activity? I'd have to look into it but when I skimmed through it I see nothing relating to having any effect on it.

 

Other DRIs[edit]

• Chaenomeles speciosa (Flowering Quince)^[9]
• Oroxylin A (found in Oroxylum indicum and Scutellaria baicalensis (Skullcap))^[10]
• Kavain and desmethoxyyangonin (possibly) (found in Piper methysticum (Kava))

 

http://en.wikipedia....ptake_inhibitor

 

BTW, I may have found the cure for my unmotivation in Kava but my "novelty seeking" DRD4 "defect" seems to make me want to seek out more shit I think I need to try out. LOL. You should see my cabinet full of drugs and supplements!

 

Sorry, I was in a bit of an altered state when I wrote the last post.

Sadly, no one human ever seems to have tried A-412,997 - can't find anyone, even among the cheminauts on the internet. The erection side-effect is indeed dose-dependent - however, there is a significant overlap between the cognitive and penile effects, which seems to make avoiding this side-effect very difficult for the majority of users. I.e, most effective doses gave the test-animals major boners, so the chances of it not giving any of us this side-effect are probably pretty slim.

 

I suggest instead that you check out Ro10-5824, which is a drug similar to A-412,997, but acts somewhat less selectively for DRD4 than A-412,997 ( but still significantly more on DRD4 than the other receptors) - apparently that drug DOESN'T have the penile side-effect! : D The reason for this, is because it seems to only be a partial agonist, instead of a full one.

As far as I know, every known dopamine reuptake inhibitor also have Norepinephrine -reuptake effects - however, some are certainly far more selective than methylphenidate or Amphetamine.

Amineptine is a drug that apparently have a pretty high affinity towards Dopamine compared to Norepinephrine, but it's also much, much weaker than traditional NDRI's, such as Methylphenidate. Still, I've seen some reports online that some people with ADHD find that it helps.

 

 

I gotta' admit, I was sceptical about using natural extracts as treatment at first, but checking out the links you had up there,  one of them does stick out to me - Flowering Quince. Apparently, the Chinese find it to be quite selective for Dopamine reuptake inhibition, over Norepinephrine, and seems to be trying to develop it into an Antiparkinson -drug. Flowering Quince might actually be worth a look. = )

Edited by Stinkorninjor, 11 March 2015 - 08:23 PM.

[eon]

Lots of people tried flowering quince with different opinions because for one they either got a different type of species or different extract or simply a different brand that didn't work out. Best is to try a variety of brands. This thread I participate on has more info on Chaenomeles Speciosa:

 

http://www.longecity...a-inhibits-dat/

Edited by eon, 11 March 2015 - 08:38 PM.

[eon]

The list of ADHD medication on drugs.com also listed Pycnogenol (as off label treatment). I've never tried Pycnogenol yet, but it's a French Maritime Pine Bark extract. The study below also have a claim of its benefit for ADHD sufferers. There was a mention of it having catechin and epicatechin, so I was wondering if those 2 may have something to do with it being beneficial for ADHD sufferers.

 

http://www.ncbi.nlm....pubmed/11996210

[Mind_Paralysis]

Pycnogenol, huh? Well, this study, which was actually double-blind etc, actually found that it was more effective than Placebo for a majority of ADHD child-patients:

 

Treatment of ADHD with French maritime pine bark extract, Pycnogenol.

http://www.ncbi.nlm....pubmed/16699814

 

This then, which have actually been TESTED for ADHD, and found effective, might be the ticket. And since it's french, it might be more reliable than Chinese supplements.

 

Or maybe not, as this site lists all the tests etc, and doesn't find it to be very effective.

 

http://examine.com/s...nts/Pycnogenol/

 

 

Some evidence that standard doses of Pycnogenol can aid in attention, but the degree of efficacy appears to be low and tends to border statistical significance at time

 

[eon]

actually if you looked again the second link you posted also have the same info. found in the first link you posted that Pycnogenol is actually effective for ADHD sufferers, it even improves mood and executive function. One way for me to find out is to try it. 

 

4.2. Attention

 

Pycnogenol, at 1mg/kg bodywright taken once daily in 61 children with confirmed ADHD for 4 weeks was associated with improvements in hyperactivity and attention when compared to both placebo and baseline (assessed by CAP rating scale); this effect was transient and the benefit returned to baseline 1 month after cessation of treatment, and assessment by CTRS or Parent assessment barely missed statistical significnace.[34] This was a replication of a previous pilot study showing greater benefits in children, but powered to a lesser degree.[35] Although the mechanism is unknown, one study noted that adrenaline concentrations in urine correlated with degree of symptoms of ADHD and that supplementation Pycnogenol at 1mg/kg bodyweight was able to decrease catecholamines in the urine (dopamine significantly, adrenaline and noradrenaline trended to significance).[36]

One study in otherwise healthy students consuming Pycnogenol for 8 weeks reported an increase in attention.[37] When another study following a comparative design tested Pycnogenol against Methylphenidate (Ritalin), surprisingly both treatments failed to outperform placebo.[38]

 Some evidence that standard doses of Pycnogenol can aid in attention, but the degree of efficacy appears to be low and tends to border statistical significance at time

 

4.3. Cognition

 

In a study on otherwise healthy students, Pycnogenol for a period of 8 weeks was associated with reduced rate of test failures and increased, memory, executive functions and mood.[37]

Edited by eon, 13 March 2015 - 07:31 PM.

[eon]

Some interesting articles on fish oil and ADHD:

 

Can Fish Oil Help Boys With ADHD Pay Attention?

 

http://www.medicinen...ticlekey=187535

 

Omega-3 Supplements May Help Boys with ADHD

 

http://news.yahoo.co...TA0XzEEc2VjA3Nj

[eon]

I'm curious if one does not have the physical proof that one has ADHD by way of a cat scan, etc. but more from verbal evaluation, which means it doesn't mean one has ADHD at all but if one uses amphetamines WITHOUT the physical proof that one has ADHD but more from verbal evaluation/diagnosis, does this mean that the prescribed ADHD drug (amphetamine) is really acting just as a stimulant? Will this then be acting as a nootropic or smart drug rather than a "medical drug" to treat a condition? This is an opinion type question/inquiry so what do you all think?

 

My ADHD diagnosis was from verbal evaluation, no cat scans to see if anything is wrong with my brain the way they do with some conditions.

[Mind_Paralysis]

Well... if it's only from the verbal evaluation, then yeah, it's not full-proof. There are often instances of misdiagnosis when it comes to neuro-psychiatric disorders - most notably the confusing between bipolar, ADHD and borderline -disorders. They all share certain symptoms, which can make it so that you receive the wrong diagnosis.

 

One way however, that might give you MORE data, is to test your dna via 23andme.com, and then download your raw genetic data, and plug it into the service Promethease - you can then get a list of certain genetic polymorphisms that you have - and because of newer research, we know actually know a few genes that increase the risk of certain NPD's - like ADHD.

 

Neither the verbal testing or the genetic one is full-proof, but they can be used to complement each other, and give you more clues as to the most fitting treatment for you, in perticular.

 

I myself were diagnosed with the verbal test, and then did the genetic testing to try and find out more - turns out I have more than 20 genes that should DECREASE the risk of ADHD, but I also have 4 genes that increase the risk substantially - out of those 4, one of them was the DRD4-mutation.

 

 

So, at least in my case, I now have a decent idea on which parts of my brain to aim the bullets at - a D4-agonist should do the trick.

 

One bullet. One kill.

 

 

( man I love that quote! Tremendous, tremendous video-game, that one.)

[chris87]

I don't mean to derail the thread, but how do I know if I have the DRD4 mutation? I looked at my 23andMe raw data, and I see that I have Rs1800955 (C;C). I'm not sure if I searched the correct SNP.

Edited by chris87, 29 April 2015 - 07:07 PM.

[YosefANaumovich]

Well... if it's only from the verbal evaluation, then yeah, it's not full-proof. There are often instances of misdiagnosis when it comes to neuro-psychiatric disorders - most notably the confusing between bipolar, ADHD and borderline -disorders. They all share certain symptoms, which can make it so that you receive the wrong diagnosis.

 

One way however, that might give you MORE data, is to test your dna via 23andme.com, and then download your raw genetic data, and plug it into the service Promethease - you can then get a list of certain genetic polymorphisms that you have - and because of newer research, we know actually know a few genes that increase the risk of certain NPD's - like ADHD.

 

Neither the verbal testing or the genetic one is full-proof, but they can be used to complement each other, and give you more clues as to the most fitting treatment for you, in perticular.

 

I myself were diagnosed with the verbal test, and then did the genetic testing to try and find out more - turns out I have more than 20 genes that should DECREASE the risk of ADHD, but I also have 4 genes that increase the risk substantially - out of those 4, one of them was the DRD4-mutation.

 

 

So, at least in my case, I now have a decent idea on which parts of my brain to aim the bullets at - a D4-agonist should do the trick.

 

One bullet. One kill.

 

 

( man I love that quote! Tremendous, tremendous video-game, that one.)

This sounds too good to be true. Does the DNA data ("raw data") they gather include unknown/unstudied genes - the WHOLE DNA code? 

Take this example: 10 years from now I use the 23andme's DNA data sheet in some program or website to test for genetic defects. Will those 10 years of research that the software or website has incorporated be able to tell me anything new, assuming anything new is found out?

[eon]

but all those disorders you mentioned sometimes co-exist with ADHD. Sometimes it's really just ADHD. My brother was diagnosed paranoid schizophrenia without the consistency of any symptoms of it (i.e. hearing voices, talking to himself, etc. none, ZERO!), but I think he was more ADHD. 

 

Wiki ADHD and see for yourself of what disorders it may co-exist with or sometimes misdiagnosed for something else than JUST ADHD. So why not let someone get on a dopaminergic/norepinephrinergic like ADHD medications and make someone happy or feel better? LOL. Even drugs.com listed armodafinil (nuvigil) as a treatment for bi polar. It is a stimulant, not your typical bipolar meds which are downers like antipsychotics that will make you feel more shitty.

 

Not sure how a website 23andme.com would determine if anything is wrong with me? Is it more like a hunch and "random" computer generator type of thing? Wouldn't a cat scan/blood test reveal a clearer picture? And even so would you use amphetamines without ADHD but more as a nootropic (expensive one)? I WOULD. Paul Erdos would. LOL. Would you?

 

Is 23andme.com free?

 

 

Well... if it's only from the verbal evaluation, then yeah, it's not full-proof. There are often instances of misdiagnosis when it comes to neuro-psychiatric disorders - most notably the confusing between bipolar, ADHD and borderline -disorders. They all share certain symptoms, which can make it so that you receive the wrong diagnosis.

 

One way however, that might give you MORE data, is to test your dna via 23andme.com, and then download your raw genetic data, and plug it into the service Promethease - you can then get a list of certain genetic polymorphisms that you have - and because of newer research, we know actually know a few genes that increase the risk of certain NPD's - like ADHD.

 

Neither the verbal testing or the genetic one is full-proof, but they can be used to complement each other, and give you more clues as to the most fitting treatment for you, in perticular.

 

I myself were diagnosed with the verbal test, and then did the genetic testing to try and find out more - turns out I have more than 20 genes that should DECREASE the risk of ADHD, but I also have 4 genes that increase the risk substantially - out of those 4, one of them was the DRD4-mutation.

 

 

So, at least in my case, I now have a decent idea on which parts of my brain to aim the bullets at - a D4-agonist should do the trick.

 

One bullet. One kill.

 

 

( man I love that quote! Tremendous, tremendous video-game, that one.)

 

Edited by eon, 29 April 2015 - 08:46 PM.